If your home is in Florida or Alaska, let's face it: Old Man Winter will move in less than three weeks from now - on Dec. 22. That's the signal to activate the central heating system, fire up the fuel-burning stoves, even snuggle down under the warmth of an electric blanket.
A hyper-high-tech, warmth-seeking strategy based on nanogram shells is heralded in a recent issue of the Proceedings of the National Academy of Sciences (PNAS) dated Oct. 28, 2003. Its title: "Nanoshell-mediated near-infrared thermal therapy of tumor under magnetic resonance guidance."
The paper's senior author is electrical engineer and chemist Naomi Halas, a chaired professor of bioengineering at Rice University in Houston. Her co-senior author is associate professor Jennifer West. "Our basic message in this PNAS paper," Halas told BioWorld Today, "is that nanoshells can be used for localized hyperthermia, which is useful for cancer therapy. That's what the article is all about. Its novelty," she continued, "is the use of a new nanoparticle called nanoshells,' which I invented about five years ago."
"The new thing about nanoshells," Halas explained, "is that they have a very strong optical resonance, which is tunable. Because they are metal, namely gold, when they absorb light they can convert it to heat. In addition to this, they could be tuned to a region of the spectrum where the body is most transparent. We can tune them down to the near-infrared window where light can penetrate the human or mouse body several centimeters deep. So in principle one can think about doing this very localized heating by depositing nanoshells at a region of a tumor site, for example, shining light through the affected body, which would heat the tumor site locally.
"This would perform thermal ablative therapy in a minimally invasive nature. Thermal therapeutic procedures are relatively simple to perform," Halas pointed out, "so have the potential of improving recovery times and reducing complication ratios and hospital stays, thus making it possible to ensure the complete thermal destruction of tumors in future studies."
Priority Biomedical Target: Breast Cancer
"An estimated 3 million women in the U.S. have breast cancer," Halas observed, "and 1 million are not yet aware of their condition. That malignancy will claim a predicted 40,000 lives in the U.S. this year. Our Innovator Award research team hopes to develop nanoshells as a platform technology for the integrated discovery, diagnosis and treatment of breast cancer. Ultimately, Jennifer West and our colleagues hope to find cancerous lumps six to seven years earlier than today's mammograms, diagnose those lumps without invasive biopsies, and destroy malignant tumors without surgery.
"She and I are studying several noninvasive medical applications for nanoshells, including photothermal treatments for cancer, implantable photoactivated drug-delivery systems, light-activated tissue welding' for wound closure, and a method for conducting rapid whole-blood immunoassays.
"Unlike drug-based cancer therapies," Halas noted, "the photothermal treatment of cancer relies on the basic physics of light. By shining near-infrared illumination on gold-coated nanoshells, doctors can generate enough heat to burst the wall of cells. The light itself is invisible and harmless. It only affects cells immediately adjacent to the nanoshells. Its use avoids many of the side effects of chemotherapy and radiation in current use, which often affect healthy tissues and make patients sick.
"Targeting nanoshells to tumor cells is accomplished in several ways," Halas noted. "The vascular systems of tumors are natural collection points for nanoshells. By attaching antibodies to their surfaces, West and I have developed cell- and tissue-specific nanoshells that can be used for therapy as well as for the optical identification of malignant cells or tissue.
"Nanoshells," Halas explained, "are metalo-dielectric nanoparticles, only slightly larger than molecules. They are concentric spheres consisting of a glass core under a thin gold shell or sheath. One tunes the optical properties by varying the relative size of the core and the gold shell. The particles are about 100 nanometers in diameter, 20 times smaller than a red blood cell - which is one/forty-millionth of an inch.
"Jennifer West has done preliminary animal experiments," Halas volunteered, "and we feel very positive about the results. Blood is transparent, for example, in this region, so it's a kind of window into the body," she went on. "We show in this paper, in cell and tissue culture, that heating could be done, also the heat profiles. We induced cancer into the tissues of the mice. Temperatures inside the tumors reached levels high enough to damage cells within four to six minutes, killing them but leaving surrounding tissue unharmed.
"We discovered this core-shell structure," Halas recounted, "in the context of working with a naturally occurring nanoparticle. Then we studied the optical properties of this system, and found that people had predicted its properties 50 years ago, but nobody had actually made such a structure. Then we began to do the theory on that particle. We understood how powerful this was if we could reliably control the structure of a core-shell nanoparticle where the gold metal was the shell. Then we figured out a way to tune the resonance over a huge amount of the spectrum across the visible and the infrared the whole way out to the far infrared."
Do-It-Themselves Leading To Patents
"That's when we realized that what we needed to do was build the particles ourselves," she said. "We've developed a nano-fabrication for doing this. One didn't exist but there was a hybrid of procedures that we adopted from different areas in chemistry that we could bring to bear on solving this problem - which we did. This was patented by Rice University; we have a composition of matter on it. It's my understanding that human clinical trials are being organized, and will take place within a year. The company developing this is Nanospectra Biosciences, in Houston.
"One thing," Halas summed up, "nanoshells are ideal for is a variety of applications within biomedicine and biotechnology. Things related to assays that can be done in whole blood. Using various sensors, we are looking for ways to sense and detect information on how individual proteins and peptides convert structural information to optical information at the single-molecule level. Cancer therapy is just one thing - though a big thing," Halas concluded.